Many biological processes are mediated by proteins participating in signal transduction pathways that involve G-proteins and/or second messengers. G-protein coupled receptors are plasma membrane proteins capable of transducing signals across a cell membrane so as to initiate a second messenger response. To this end, the G-protein coupled receptors bind a variety of ligands ranging from small biogenic amines to peptides, small proteins and large glycoproteins (C. D. Strader et al., Annu. Rev. Biochem. 63, 101-132 (1994)). All G-protein coupled receptors have been characterized as having seven hydrophobic domains, which have been postulated to span the plasma membrane, connected by hydrophilic extracellular and intracellular loops. The G-protein family of coupled receptors includes dopamine, calcitonin, adrenergic, endothelin, CAMP, adenosine, serotonin, follicle stimulating hormone, opsin and rhodopsin receptors.
G-protein coupled receptors can be intracellularly coupled to various intracellular enzymes, ion channels and transporters. Different G-protein .alpha.-subunits preferentially stimulate particular effectors to modulate various biological functions in a cell. Phosphorylation of cytoplasmic residues of G-protein coupled receptors have been identified as an important mechanism for the regulation of G-protein coupling of the G-protein coupled receptors.